8D1K

hBest1 Ca2+-bound partially open neck state

Summary for 8D1K

• Entry DOI: 10.2210/pdb8d1k/pdb
• EMDB information: 27127 27128 27129 27130 27131 27132 27133 27134 27135 27136 27137
• Descriptor: Bestrophin-1, CALCIUM ION, 1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE (3 entities in total)
• Functional Keywords: ion channel, chloride channel, anion channel, pentamer, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 5
• Total formula weight: 366120.05

Authors

Owji, A.P.,Kittredge, A.,Hendrickson, W.A.,Tingting, Y. (deposition date: 2022-05-27, release date: 2022-07-13, Last modification date: 2024-02-14)

Primary citation

Owji, A.P.,Wang, J.,Kittredge, A.,Clark, Z.,Zhang, Y.,Hendrickson, W.A.,Yang, T.
Structures and gating mechanisms of human bestrophin anion channels.
Nat Commun, 13:3836-3836, 2022

PubMed Abstract: Bestrophin-1 (Best1) and bestrophin-2 (Best2) are two members of the bestrophin family of calcium (Ca)-activated chloride (Cl) channels with critical involvement in ocular physiology and direct pathological relevance. Here, we report cryo-EM structures of wild-type human Best1 and Best2 in various states at up to 1.8 Å resolution. Ca-bound Best1 structures illustrate partially open conformations at the two Ca-dependent gates of the channels, in contrast to the fully open conformations observed in Ca-bound Best2, which is in accord with the significantly smaller currents conducted by Best1 in electrophysiological recordings. Comparison of the closed and open states reveals a C-terminal auto-inhibitory segment (AS), which constricts the channel concentrically by wrapping around the channel periphery in an inter-protomer manner and must be released to allow channel opening. Our results demonstrate that removing the AS from Best1 and Best2 results in truncation mutants with similar activities, while swapping the AS between Best1 and Best2 results in chimeric mutants with swapped activities, underlying a key role of the AS in determining paralog specificity among bestrophins.

PubMed: 35789156
DOI: 10.1038/s41467-022-31437-7

Experimental method

ELECTRON MICROSCOPY (2.28 Å)